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Erythropoietin regulates the expression of dimeric form of acetylcholinesterase during differentiation of erythroblast
Author(s) -
Xu Miranda L.,
Luk Wilson K. W.,
Bi Cathy W. C.,
Liu Etta Y. L.,
Wu Kevin Q. Y.,
Yao Ping,
Dong Tina T. X.,
Tsim Karl W. K.
Publication year - 2018
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14448
Subject(s) - acetylcholinesterase , microbiology and biotechnology , transcription factor , biology , erythropoietin , erythropoiesis , chemistry , gene , biochemistry , enzyme , medicine , endocrinology , anemia
Acetylcholinesterase ( AC hE; EC 3.1.1.7) is known to hydrolyze acetylcholine at cholinergic synapses. In mammalian erythrocyte, AC hE exists as a dimer (G 2 ) and is proposed to play role in erythropoiesis. To reveal the regulation of AC hE during differentiation of erythroblast, erythroblast‐like cells ( TF ‐1) were induced to differentiate by application of erythropoietin ( EPO ). The expression of AC hE was increased in parallel to the stages of differentiation. Application of EPO in cultured TF ‐1 cells induced transcriptional activity of ACHE gene, as well as its protein product. This EPO ‐induced event was in parallel with erythrocytic proteins, for example, α‐ and β‐globins. The EPO ‐induced AC hE expression was mediated by phosphorylations of Akt and GATA ‐1; because the application of Akt kinase inhibitor blocked the gene activation. Erythroid transcription factor also known as GATA ‐1, a downstream transcription factor of EPO signaling, was proposed here to account for regulation of AC hE in TF ‐1 cell. A binding sequence of GATA ‐1 was identified in ACHE gene promoter, which was further confirmed by chromatin immunoprecipitation (Ch IP ) assay. Over‐expression of GATA ‐1 in TF ‐1 cultures induced AC hE expression, as well as activity of ACHE promoter tagged with luciferase gene ( pAChE ‐Luc). The deletion of GATA ‐1 sequence on the ACHE promoter, pAChE Δ GATA ‐1 ‐Luc, reduced the promoter activity during erythroblastic differentiation. On the contrary, the knock‐down of AC hE in TF ‐1 cultures could lead to a reduction in EPO ‐induced expression of erythrocytic proteins. These findings indicated specific regulation of AC hE during maturation of erythroblast, which provided an insight into elucidating possible mechanisms in regulating erythropoiesis.